{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,17]],"date-time":"2026-09-17T06:23:07Z","timestamp":1789626187830,"version":"build-2803163510"},"reference-count":147,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T00:00:00Z","timestamp":1740009600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes"],"abstract":"<jats:p>Down syndrome (DS), the most common survivable autosomal aneuploidy, is associated with a high prevalence of congenital anomalies of the kidney and urinary tract (CAKUT), significantly increasing the risk of chronic kidney disease (CKD). This review examines the diversity of CAKUT phenotypes reported in individuals with DS, focusing on anomalies affecting the kidney, ureter, bladder, and urethra. According to available literature, hydronephrosis is the most common renal anomaly, often secondary to other CAKUT phenotypes, followed by renal hypoplasia and glomerulocystic disease. Furthermore, obstructive uropathies are also frequent but usually lack detailed characterization in the literature. Key features of CAKUT in DS, including reduced kidney size, renal cystic diseases, acquired glomerulopathies, reduced nephron number, and immature glomeruli heighten the risk of CKD. Also, early detection of lower urinary tract dysfunction (LUTD) is critical to prevent progressive upper urinary tract damage and CKD. Despite the prevalence of CAKUT in DS, reported between 0.22% and 21.16%, there is a lack of standardized diagnostic criteria, consistent terminology, and extended follow-up studies. Systematic screening from infancy, including regular renal monitoring via urinalysis and ultrasound, plays a critical role in the timely diagnosis and intervention of CAKUT. To further enhance diagnostic accuracy and develop effective therapeutic strategies, increased awareness and focused research into the genetic factors underlying these anomalies are essential. Moreover, a multidisciplinary approach is indispensable for managing CAKUT and its associated complications, ultimately ensuring better long-term outcomes and an improved quality of life for individuals with DS.<\/jats:p>","DOI":"10.3390\/genes16030245","type":"journal-article","created":{"date-parts":[[2025,2,20]],"date-time":"2025-02-20T11:03:37Z","timestamp":1740049417000},"page":"245","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Congenital Anomalies of the Kidney and Urinary Tract in Down Syndrome: Prevalence, Phenotypes, Genetics and Clinical Management"],"prefix":"10.3390","volume":"16","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-7741-4768","authenticated-orcid":false,"given":"Mirela","family":"Leskur","sequence":"first","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-5126-3869","authenticated-orcid":false,"given":"Dario","family":"Leskur","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2259-2871","authenticated-orcid":false,"given":"Sandra","family":"Marijan","sequence":"additional","affiliation":[{"name":"Department of Biochemistry and Medical Chemistry, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4867-3648","authenticated-orcid":false,"given":"Luka","family":"Minarik","sequence":"additional","affiliation":[{"name":"Institute of Emergency Medicine, 10000 Zagreb, Croatia"},{"name":"Department of Paediatrics, University of Split School of Medicine, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8242-0388","authenticated-orcid":false,"given":"Bernarda","family":"Lozi\u0107","sequence":"additional","affiliation":[{"name":"Department of Paediatrics, University of Split School of Medicine, 21000 Split, Croatia"},{"name":"Department of Pediatric Disease, Division of Haematology, Oncology, Clinical Immunology and Genetics, University Hospital of Split, 21000 Split, Croatia"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,2,20]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"402","DOI":"10.1038\/s41431-020-00748-y","article-title":"Estimation of the number of people with Down syndrome in Europe","volume":"29","author":"Buckley","year":"2021","journal-title":"Eur. J. Hum. Genet."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1466","DOI":"10.1126\/science.aav7321","article-title":"Chromosome errors in human eggs shape natural fertility over reproductive lifespan","volume":"365","author":"Gruhn","year":"2019","journal-title":"Science"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1038\/s41572-019-0143-7","article-title":"Down syndrome","volume":"6","author":"Antonarakis","year":"2020","journal-title":"Nat. Rev. Dis. Primers"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"2361","DOI":"10.1007\/s00467-022-05455-y","article-title":"Widespread kidney anomalies in children with Down syndrome","volume":"37","author":"Postolache","year":"2022","journal-title":"Pediatr. Nephrol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"143","DOI":"10.3390\/pediatric15010012","article-title":"CAKUT: A Pediatric and Evolutionary Perspective on the Leading Cause of CKD in Childhood","volume":"15","author":"Chevalier","year":"2023","journal-title":"Pediatr. Rep."},{"key":"ref_6","first-page":"54","article-title":"Observations on an ethnic classification of idiots","volume":"33","author":"Down","year":"1995","journal-title":"Ment. Retard."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1136\/hrt.22.3.331","article-title":"Congenital cardiac malformations in mongolism","volume":"22","author":"Berg","year":"1960","journal-title":"Br. Heart J."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"248","DOI":"10.1159\/000240070","article-title":"Prenatal organ and cellular growth with various chromosomal disorders","volume":"11","author":"Naeye","year":"1967","journal-title":"Biol. Neonatorum"},{"key":"ref_9","first-page":"1","article-title":"Malformations of kidney and urinary tract in common chromosomal aberrations. I. Clinical studies","volume":"18","author":"Egli","year":"1973","journal-title":"Humangenetik"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"879","DOI":"10.3109\/15513819109065484","article-title":"The urinary system in Down syndrome: A study of 124 autopsy cases","volume":"11","author":"Ariel","year":"1991","journal-title":"Pediatr. Pathol."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1007\/BF00860766","article-title":"Renal anomalies in Down syndrome","volume":"9","author":"Subrahmanyam","year":"1995","journal-title":"Pediatr. Nephrol."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"329","DOI":"10.1053\/ajkd.1998.v31.pm9469506","article-title":"Renal disease in Down syndrome: Autopsy study with emphasis on glomerular lesions","volume":"31","author":"Lo","year":"1998","journal-title":"Am. J. Kidney Dis."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"614","DOI":"10.1007\/s00467-005-1825-9","article-title":"Renal involvement in Down syndrome","volume":"20","author":"Pardo","year":"2005","journal-title":"Pediatr. Nephrol."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"369","DOI":"10.1016\/j.jpurol.2007.02.003","article-title":"Is there an association between functional bladder outlet obstruction and Down\u2019s syndrome?","volume":"3","author":"Hicks","year":"2007","journal-title":"J. Pediatr. Urol."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1007\/s00120-007-1614-0","article-title":"Urological manifestations of Down syndrome: Significance and long-term complications\u2014Our own patient cohort with an overview","volume":"47","author":"Ebert","year":"2008","journal-title":"Urologe"},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"209","DOI":"10.1097\/MCD.0b013e32833b2b9c","article-title":"Consideration of VACTERL association in patients with trisomy 21","volume":"19","author":"Solomon","year":"2010","journal-title":"Clin. Dysmorphol."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"734","DOI":"10.1007\/s12098-013-1244-z","article-title":"Evaluation of structural anomalies of kidney and urinary tract in children with Down syndrome","volume":"81","author":"Jain","year":"2014","journal-title":"Indian. J. Pediatr."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"40","DOI":"10.1177\/000992288702600107","article-title":"Hypospadias and urethral abnormalities in Down syndrome","volume":"26","author":"Lang","year":"1987","journal-title":"Clin. Pediatr."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"e615","DOI":"10.1542\/peds.2009-0181","article-title":"Increased prevalence of renal and urinary tract anomalies in children with Down syndrome","volume":"124","author":"Kupferman","year":"2009","journal-title":"Pediatrics"},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1172\/JCI95300","article-title":"Genetic basis of human congenital anomalies of the kidney and urinary tract","volume":"128","author":"Westland","year":"2018","journal-title":"J. Clin. Investig."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"987","DOI":"10.1016\/j.ajhg.2012.10.007","article-title":"Copy-Number Disorders Are a Common Cause of Congenital Kidney Malformations","volume":"91","author":"Kiryluk","year":"2012","journal-title":"Am. J. Hum. Genet."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"525","DOI":"10.1111\/nep.14190","article-title":"Renal agenesis: A meta-analysis of its prevalence and clinical characteristics based on 15,641,184 patients","volume":"28","author":"Plutecki","year":"2023","journal-title":"Nephrology"},{"key":"ref_23","first-page":"962","article-title":"Chromosomic diagnosis of mongolism","volume":"16","author":"Lejeune","year":"1959","journal-title":"Arch. Fr. Pediatr."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1186\/s13052-024-01636-7","article-title":"Kidney and urogenital abnormalities in Down syndrome: A meta-analysis","volume":"50","author":"Rossetti","year":"2024","journal-title":"Ital. J. Pediatr."},{"key":"ref_25","unstructured":"Savva, G.M., Morris, J.K., Mutton, D.E., and Alberman, E. (2024, June 24). Maternal Age-Specific Fetal Loss Rates in Down Syndrome Pregnancies. Available online: https:\/\/obgyn.onlinelibrary.wiley.com\/doi\/10.1002\/pd.1443."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"952","DOI":"10.1080\/14767058.2018.1511695","article-title":"The role of fetal growth restriction in the association between Down syndrome and perinatal mortality","volume":"33","author":"Yao","year":"2020","journal-title":"J. Matern.-Fetal Neonatal Med."},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"2979","DOI":"10.1002\/ajmg.a.36780","article-title":"Major congenital anomalies in babies born with Down syndrome: A EUROCAT population-based registry study","volume":"164","author":"Morris","year":"2014","journal-title":"Am. J. Med. Genet. Part A"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"723","DOI":"10.2215\/CJN.12581019","article-title":"A Primer on Congenital Anomalies of the Kidneys and Urinary Tracts (CAKUT)","volume":"15","author":"Murugapoopathy","year":"2020","journal-title":"Clin. J. Am. Soc. Nephrol. CJASN"},{"key":"ref_29","first-page":"79","article-title":"Epidemiology of Down syndrome in 118,265 consecutive births","volume":"7","author":"Stoll","year":"1990","journal-title":"Am. J. Med. Genet."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1002\/(SICI)1096-8628(19961016)65:2<160::AID-AJMG16>3.0.CO;2-O","article-title":"Major congenital malformations in Down syndrome","volume":"65","author":"Mastroiacovo","year":"1996","journal-title":"Am. J. Med. Genet."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"431","DOI":"10.1002\/(SICI)1096-8628(19980605)77:5<431::AID-AJMG15>3.0.CO;2-J","article-title":"Anomalies in Down syndrome individuals in a large population-based registry","volume":"77","author":"Torfs","year":"1998","journal-title":"Am. J. Med. Genet."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"657","DOI":"10.1002\/bdra.20393","article-title":"Congenital defects among liveborn infants with Down syndrome","volume":"79","author":"Cleves","year":"2007","journal-title":"Birth Defects Res. Part A\u2014Clin. Mol. Teratol."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"e1373","DOI":"10.1542\/peds.2011-3051","article-title":"Predictors of survival in children born with Down syndrome: A registry-based study","volume":"129","author":"Rankin","year":"2012","journal-title":"Pediatrics"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"674","DOI":"10.1016\/j.ejmg.2015.11.003","article-title":"Associated congenital anomalies among cases with Down syndrome","volume":"58","author":"Stoll","year":"2015","journal-title":"Eur. J. Med. Genet."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"1","DOI":"10.21767\/AMJ.2017.3152","article-title":"Incidence and outcome of renal anomalies in children with down syndrome","volume":"11","author":"Safdar","year":"2018","journal-title":"Australas. Med. J."},{"key":"ref_36","unstructured":"(2024, November 11). Congenital Malformations Worldwide: A Report from the International Clearinghouse for Birth Defects Monitoring Systems | GHDx. Available online: https:\/\/ghdx.healthdata.org\/record\/congenital-malformations-worldwide-report-international-clearinghouse-birth-defects."},{"key":"ref_37","first-page":"477","article-title":"Potter syndrome caused by bilateral renal agenesis and duodenal atresia","volume":"58","author":"Insunza","year":"1993","journal-title":"Rev. Chil. Obstet. Ginecol."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"112","DOI":"10.1159\/000168285","article-title":"Mesangiocapillary glomerulonephritis in Down\u2019s syndrome","volume":"11","author":"Gupta","year":"1991","journal-title":"Am. J. Nephrol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"429","DOI":"10.1007\/s12291-013-0308-1","article-title":"Down syndrome with end-stage renal disease","volume":"28","author":"Kute","year":"2013","journal-title":"Indian. J. Clin. Biochem."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"359","DOI":"10.3109\/01443615.2015.1065232","article-title":"Contribution of post-mortem MRI to the evaluation of subtle renal anomalies in a first trimester foetus with Down syndrome","volume":"36","author":"Staicu","year":"2016","journal-title":"J. Obstet. Gynaecol."},{"key":"ref_41","first-page":"33","article-title":"Thoracic ectopic right kidney associated with Down syndrome and a serious heart abnormality","volume":"6","author":"Boronat","year":"1982","journal-title":"Actas Urol. Esp."},{"key":"ref_42","first-page":"166","article-title":"Right intrathoracic renal ectopia: A case report and review of the literature","volume":"5","author":"Stein","year":"1999","journal-title":"Tech. Urol."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1002\/ppul.20253","article-title":"Unusual cause of lung and renal disease in a baby with trisomy 21","volume":"40","author":"Navarro","year":"2005","journal-title":"Pediatr. Pulmonol."},{"key":"ref_44","first-page":"354","article-title":"A three-year old girl with Down\u2019s syndrome and an abnormal finding in the chest","volume":"25","year":"2005","journal-title":"Ann. Saudi Med."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"322","DOI":"10.4103\/1319-2442.109593","article-title":"Hemodialysis treatment on an adult patient with Down syndrome associated with ectopic right kidney chronic obstructive nephropathy and secondary amyloidosis","volume":"24","author":"Kosmadakis","year":"2013","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_46","first-page":"46","article-title":"Kidney trasplantation in a female infant with Down syndrome, Pseudo Prune Belly Syndrome, and a post-transplant lymphoproliferative disorder. First case report in Argentina","volume":"43","author":"Anriquez","year":"2023","journal-title":"Rev. Nefrol. Dial. Traspl."},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"771","DOI":"10.1007\/BF01213350","article-title":"Renal replacement therapy in Down\u2019s syndrome","volume":"7","author":"Webb","year":"1993","journal-title":"Pediatr. Nephrol."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"802","DOI":"10.1007\/BF02734159","article-title":"Posterior urethral valves in patients with Down syndrome","volume":"72","author":"Narasimhan","year":"2005","journal-title":"Indian. J. Pediatr."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"15","DOI":"10.1016\/j.jpeds.2007.09.045","article-title":"Prevalence, neonatal characteristics, and first-year mortality of Down syndrome: A national study","volume":"152","author":"Weijerman","year":"2008","journal-title":"J. Pediatr."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"e15145","DOI":"10.1097\/MD.0000000000015145","article-title":"End-stage renal disease in a Down syndrome patient caused by delayed diagnosis of nonneurogenic bladder: A case report","volume":"98","author":"Kim","year":"2019","journal-title":"Medicine"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"644","DOI":"10.1007\/BF00858153","article-title":"Chronic peritoneal dialysis in a child with Down syndrome","volume":"8","author":"Kupferman","year":"1994","journal-title":"Pediatr. Nephrol."},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"484","DOI":"10.1159\/000063317","article-title":"A Down syndrome patient treated by peritoneal dialysis","volume":"92","author":"Hausmann","year":"2002","journal-title":"Nephron"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"4","DOI":"10.1016\/j.afju.2015.01.001","article-title":"Posterior urethral valves and Down syndrome","volume":"21","author":"Lazarus","year":"2015","journal-title":"Afr. J. Urol."},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"637.e1","DOI":"10.1016\/j.jpurol.2023.04.002","article-title":"Posterior urethral valves in patients with trisomy 21: Similar renal outcomes and rates of volitional voiding","volume":"19","author":"Xiang","year":"2023","journal-title":"J. Pediatr. Urol."},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"558","DOI":"10.1177\/089686080802800526","article-title":"Chronic peritoneal dialysis treatment in a pediatric patient with Down syndrome","volume":"28","author":"Yavascan","year":"2008","journal-title":"Perit. Dial. Int."},{"key":"ref_56","doi-asserted-by":"crossref","unstructured":"Gearhart, J.P., and Mathews, R. (1999). Anatomy of Cloacal Exstrophy. The Exstrophy\u2014Epispadias Complex: Research Concepts and Clinical Applications, Springer.","DOI":"10.1007\/978-1-4757-3056-2"},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"566","DOI":"10.1007\/s00431-006-0116-1","article-title":"MTHFR 677 TT genotype in a mother and her child with Down syndrome, atrioventricular canal and exstrophy of the bladder: Implications of a mutual genetic risk factor?","volume":"165","author":"Reutter","year":"2006","journal-title":"Eur. J. Pediatr."},{"key":"ref_58","unstructured":"Potter, E.L. (1972). Normal and Abnormal Development of the Kidney, Year Book Medical Publishers."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"298","DOI":"10.4103\/1319-2442.202767","article-title":"Biopsy of small kidneys: A safe and a useful guide to potentially treatable kidney disease","volume":"28","author":"Varro","year":"2017","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1501","DOI":"10.1007\/s00467-015-3079-5","article-title":"The impact of small kidneys","volume":"30","author":"Matsell","year":"2015","journal-title":"Pediatr. Nephrol."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"321","DOI":"10.1016\/j.path.2014.04.008","article-title":"Autopsy Renal Pathology","volume":"7","author":"Paueksakon","year":"2014","journal-title":"Surg. Pathol. Clin."},{"key":"ref_62","doi-asserted-by":"crossref","unstructured":"Rowe, C.K., and Merguerian, P.A. (2024). Developmental Abnormalities of the Genitourinary System. Avery\u2019s Diseases of the Newborn, Elsevier.","DOI":"10.1016\/B978-0-323-82823-9.00076-3"},{"key":"ref_63","doi-asserted-by":"crossref","unstructured":"Rosenblum, N.D. (2018). Kidney Development. National Kidney Foundation\u2019s Primer on Kidney Diseases, Elsevier.","DOI":"10.1016\/B978-0-323-47794-9.00002-0"},{"key":"ref_64","unstructured":"Pandya, P.P., Oepkes, D., Sebire, N.J., and Wapner, R.J. (2020). 33\u2014Kidney and Urinary Tract Disorders. Fetal Medicine, Elsevier. [3rd ed.]. Available online: https:\/\/www.sciencedirect.com\/science\/article\/pii\/B9780702069567000336."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"1306","DOI":"10.2214\/AJR.15.14625","article-title":"Incidence and Spectrum of Renal Complications and Extrarenal Diseases and Syndromes in 380 Children and Young Adults With Horseshoe Kidney","volume":"205","author":"Je","year":"2015","journal-title":"AJR Am. J. Roentgenol."},{"key":"ref_66","unstructured":"Goksu, S.Y., Leslie, S.W., and Khattar, D. (2024, November 06). Renal Cystic Disease, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK554504\/."},{"key":"ref_67","first-page":"e050125","article-title":"Morphological changes in the kidney of fetuses with Down syndrome","volume":"5","author":"Desogus","year":"2016","journal-title":"J. Pediatr. Neonatal Individ. Med."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"37","DOI":"10.1093\/ndt\/17.suppl_9.37","article-title":"Pathogenesis of dysplastic kidney associated with urinary tract obstruction in utero","volume":"17","author":"Nagata","year":"2002","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"1","DOI":"10.12968\/hmed.2019.0274","article-title":"An overview of hydronephrosis in adults","volume":"81","author":"Patel","year":"2020","journal-title":"Br. J. Hosp. Med."},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"132","DOI":"10.1002\/uog.5224","article-title":"Choroid plexus cyst, intracardiac echogenic focus, hyperechogenic bowel and hydronephrosis in screening for trisomy 21 at 11 + 0 to 13 + 6 weeks","volume":"31","author":"Dagklis","year":"2008","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_71","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1053\/j.semperi.2015.11.009","article-title":"Ultrasound screening: Status of markers and efficacy of screening for structural abnormalities","volume":"40","author":"Rao","year":"2016","journal-title":"Semin. Perinatol."},{"key":"ref_72","doi-asserted-by":"crossref","first-page":"1849","DOI":"10.1016\/j.juro.2009.03.025","article-title":"Fetal pyelectasis as predictor of decreased differential renal function","volume":"182","author":"Kim","year":"2009","journal-title":"J. Urol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"732","DOI":"10.1016\/j.ajog.2005.02.074","article-title":"Isolated fetal pyelectasis and chromosomal abnormalities","volume":"193","author":"Coco","year":"2005","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_74","first-page":"58","article-title":"Fetal pyelectasis: A possible association with Down syndrome","volume":"76","author":"Benacerraf","year":"1990","journal-title":"Obstet. Gynecol."},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"197","DOI":"10.1046\/j.1469-0705.2001.00360.x","article-title":"The association of aneuploidy and mild fetal pyelectasis in an unselected population: The results of a multicenter study","volume":"17","author":"Chudleigh","year":"2001","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_76","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1002\/uog.12516","article-title":"Isolated fetal pyelectasis and the risk of Down syndrome: A meta-analysis","volume":"42","author":"Orzechowski","year":"2013","journal-title":"Ultrasound Obstet. Gynecol."},{"key":"ref_77","first-page":"549","article-title":"Glomerulonephritis in children with Down syndrome","volume":"10","author":"Birk","year":"1996","journal-title":"Pediatr. Nephrol."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1016\/j.humpath.2011.04.009","article-title":"Acquired glomerular lesions in patients with Down syndrome","volume":"43","author":"Said","year":"2012","journal-title":"Hum. Pathol."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"104441","DOI":"10.1016\/j.amsu.2022.104441","article-title":"Primary membranoproliferative glomerulonephritis in a child with down syndrome complicated with CVA: A case report","volume":"81","author":"Alsultan","year":"2022","journal-title":"Ann. Med. Surg."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"134","DOI":"10.1007\/s00431-005-0003-1","article-title":"Renal amyloidosis due to pulmonary tuberculosis in a patient with Down syndrome","volume":"165","author":"Ozkaya","year":"2006","journal-title":"Eur. J. Pediatr."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"86","DOI":"10.1007\/BF00861584","article-title":"Immunotactoid glomerulopathy in a child with Down syndrome","volume":"7","author":"Takemura","year":"1993","journal-title":"Pediatr. Nephrol."},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"204","DOI":"10.1007\/BF00860750","article-title":"Anti-neutrophil cytoplasmic antibody associated glomerulonephritis in a patient with Down\u2019s syndrome","volume":"9","author":"Robson","year":"1995","journal-title":"Pediatr. Nephrol."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"2142","DOI":"10.1093\/ndt\/13.8.2142","article-title":"Proteinase-3-antineutrophil cytoplasmic antibody (PR3-ANCA) positive crescentic glomerulonephritis in a patient with Down\u2019s syndrome and infectious endocarditis","volume":"13","author":"Haseyama","year":"1998","journal-title":"Nephrol. Dial. Transplant."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"249","DOI":"10.1007\/BF00862096","article-title":"A patient with Down\u2019s syndrome and anti-neutrophilic cytoplasmic antibody-positive vasculitis","volume":"10","author":"Schwab","year":"1996","journal-title":"Pediatr. Nephrol."},{"key":"ref_85","first-page":"211","article-title":"Renal transplantation in Down syndrome: A report of the North American Pediatric Renal Transplant Cooperative Study","volume":"2","author":"Baqi","year":"1998","journal-title":"Pediatr. Transplant."},{"key":"ref_86","first-page":"CS54","article-title":"IgG-associated mesangial glomerulonephritis in a patient with Down syndrome","volume":"10","author":"Assadi","year":"2004","journal-title":"Med. Sci. Monit."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"1223","DOI":"10.4103\/1319-2442.121311","article-title":"Pauci-immune crescentic glomerulonephritis in the Down\u2019s syndrome","volume":"24","author":"Cherif","year":"2013","journal-title":"Saudi J. Kidney Dis. Transpl."},{"key":"ref_88","doi-asserted-by":"crossref","unstructured":"Ferrari, M., and Stagi, S. (2021). Autoimmunity and Genetic Syndromes: A Focus on Down Syndrome. Genes, 12.","DOI":"10.3390\/genes12020268"},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.kint.2024.10.027","article-title":"The autoimmune architecture of childhood idiopathic nephrotic syndrome","volume":"107","author":"Piccirillo","year":"2025","journal-title":"Kidney Int."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"147","DOI":"10.1038\/nrg.2016.154","article-title":"Down syndrome and the complexity of genome dosage imbalance","volume":"18","author":"Antonarakis","year":"2017","journal-title":"Nat. Rev. Genet."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"956","DOI":"10.1055\/s-2006-924458","article-title":"Analysis of the neonatal collective in the Federal Republic of Germany 12th report: Presentation of detailed percentiles for the body measurement of newborns","volume":"66","author":"Voigt","year":"2006","journal-title":"Geburtshilfe Frauenheilkd."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"640","DOI":"10.1111\/ped.14140","article-title":"Renal impairment associated with oligonephronia in a patient with Down syndrome","volume":"62","author":"Wada","year":"2020","journal-title":"Pediatr. Int."},{"key":"ref_93","doi-asserted-by":"crossref","first-page":"568","DOI":"10.1007\/s10024-003-1008-2","article-title":"Renal tubular dysgenesis in an hydropic fetus with trisomy 21: A case report with literature review","volume":"6","author":"Jain","year":"2003","journal-title":"Pediatr. Dev. Pathol."},{"key":"ref_94","unstructured":"Thotakura, R., and Anjum, F. (2024, November 06). Hydronephrosis and Hydroureter, Available online: http:\/\/www.ncbi.nlm.nih.gov\/books\/NBK563217\/."},{"key":"ref_95","doi-asserted-by":"crossref","first-page":"B16","DOI":"10.1016\/j.ajog.2021.06.044","article-title":"Hydroureter","volume":"225","author":"Osmundson","year":"2021","journal-title":"Am. J. Obstet. Gynecol."},{"key":"ref_96","doi-asserted-by":"crossref","first-page":"227","DOI":"10.1097\/MOP.0000000000000994","article-title":"Ureteropelvic junction obstruction: Diagnosis and management","volume":"33","author":"Vemulakonda","year":"2021","journal-title":"Curr. Opin. Pediatr."},{"key":"ref_97","doi-asserted-by":"crossref","first-page":"318","DOI":"10.1016\/j.jpedsurg.2018.10.091","article-title":"Current epidemiology and antenatal presentation of posterior urethral valves: Outcome of BAPS CASS National Audit","volume":"54","author":"Brownlee","year":"2019","journal-title":"J. Pediatr. Surg."},{"key":"ref_98","doi-asserted-by":"crossref","first-page":"560","DOI":"10.1038\/pr.2014.134","article-title":"Epidemiology and demography of recently diagnosed cases of posterior urethral valves","volume":"76","author":"Thakkar","year":"2014","journal-title":"Pediatr. Res."},{"key":"ref_99","doi-asserted-by":"crossref","unstructured":"Tambo, F.F.M., Tolefac, P.N., Ngowe, M.N., Minkande, J.Z., Mbouche, L., Guemkam, G., Telelen, N.A., Angwafo, F.F., and Sosso, A.M. (2018). Posterior urethral valves: 10 years audit of epidemiologic, diagnostic and therapeutic aspects in Yaound\u00e9 gynaeco-obstetric and paediatric hospital. BMC Urol., 18.","DOI":"10.1186\/s12894-018-0364-1"},{"key":"ref_100","doi-asserted-by":"crossref","unstructured":"Meneghesso, D., Partigiani, N.B., Spagnol, R., Brazzale, A.R., Morlacco, A., and Vidal, E. (2023). Nadir creatinine as a predictor of renal outcomes in PUVs: A systematic review and meta-analysis. Front. Pediatr., 11.","DOI":"10.3389\/fped.2023.1085143"},{"key":"ref_101","first-page":"198ra106","article-title":"Fetal Urinary Peptides to Predict Postnatal Outcome of Renal Disease in Fetuses with Posterior Urethral Valves (PUV)","volume":"5","author":"Julie","year":"2013","journal-title":"Sci. Transl. Med."},{"key":"ref_102","doi-asserted-by":"crossref","first-page":"678","DOI":"10.1007\/BF03035427","article-title":"Posterior urethral valves in trisomy 21","volume":"10","author":"Bielek","year":"1996","journal-title":"Pediatr. Nephrol."},{"key":"ref_103","doi-asserted-by":"crossref","first-page":"403","DOI":"10.4103\/0971-4065.103922","article-title":"A case of Down syndrome with a posterior urethral valve","volume":"22","author":"Mondal","year":"2012","journal-title":"Indian. J. Nephrol."},{"key":"ref_104","doi-asserted-by":"crossref","first-page":"S181","DOI":"10.5152\/tud.2018.70852","article-title":"Congenital megalourethra and posterior urethral valve in a patient with Down syndrome","volume":"45","author":"Karaman","year":"2019","journal-title":"Turk. J. Urol."},{"key":"ref_105","doi-asserted-by":"crossref","first-page":"e240857","DOI":"10.1136\/bcr-2020-240857","article-title":"Spontaneous bladder rupture secondary to posterior urethral valves in a boy with Down syndrome","volume":"14","author":"Garriboli","year":"2021","journal-title":"BMJ Case Rep."},{"key":"ref_106","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1111\/ans.1990.60.2.113","article-title":"Vesico-ureteric reflux in Down\u2019s syndrome: Poor prognosis","volume":"60","author":"Ahmed","year":"1990","journal-title":"Aust. N. Z. J. Surg."},{"key":"ref_107","doi-asserted-by":"crossref","first-page":"e20162590","DOI":"10.1542\/peds.2016-2590","article-title":"Establishing a Standard Protocol for the Voiding Cystourethrography","volume":"138","author":"Frimberger","year":"2016","journal-title":"Pediatrics"},{"key":"ref_108","doi-asserted-by":"crossref","first-page":"783","DOI":"10.1016\/j.juro.2015.03.114","article-title":"Trends in Toilet Training and Voiding Habits among Children with Down Syndrome","volume":"194","author":"Powers","year":"2015","journal-title":"J. Urol."},{"key":"ref_109","doi-asserted-by":"crossref","first-page":"286","DOI":"10.1016\/j.jped.2017.06.011","article-title":"Prolonged toilet training in children with Down syndrome: A case\u2013control study","volume":"94","author":"Mrad","year":"2018","journal-title":"J. Pediatr."},{"key":"ref_110","doi-asserted-by":"crossref","first-page":"833","DOI":"10.1002\/nau.24293","article-title":"Evaluation of lower urinary tract symptoms in children with Down syndrome: A prospective, case-controlled cohort study","volume":"39","author":"Kalemci","year":"2020","journal-title":"Neurourol. Urodyn."},{"key":"ref_111","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1007\/s00467-023-05986-y","article-title":"Kidney and urological involvement in Down syndrome: Frequent, underestimated, but associated with impaired quality of life and risk of kidney failure","volume":"39","author":"Ranchin","year":"2024","journal-title":"Pediatr. Nephrol."},{"key":"ref_112","doi-asserted-by":"crossref","first-page":"646","DOI":"10.1016\/S0022-5347(05)63983-3","article-title":"Males with Down\u2019s syndrome and nonneurogenic neurogenic bladder","volume":"169","author":"Handel","year":"2003","journal-title":"J. Urol."},{"key":"ref_113","doi-asserted-by":"crossref","first-page":"259","DOI":"10.1002\/nau.1003","article-title":"Learned voiding dysfunction (non-neurogenic, neurogenic bladder) among adults","volume":"20","author":"Groutz","year":"2001","journal-title":"Neurourol. Urodyn."},{"key":"ref_114","doi-asserted-by":"crossref","first-page":"867","DOI":"10.1111\/j.1442-2042.2007.01848.x","article-title":"A female case with Down syndrome and non-neurogenic neurogenic bladder","volume":"14","author":"Kai","year":"2007","journal-title":"Int. J. Urol."},{"key":"ref_115","doi-asserted-by":"crossref","first-page":"902","DOI":"10.1111\/ped.12367","article-title":"Assessment of lower urinary tract function in children with Down syndrome","volume":"56","author":"Kitamura","year":"2014","journal-title":"Pediatr. Int."},{"key":"ref_116","doi-asserted-by":"crossref","first-page":"577","DOI":"10.1097\/00042307-200111000-00004","article-title":"Neurogenic and non-neurogenic bladder dysfunction","volume":"11","author":"Nijman","year":"2001","journal-title":"Curr. Opin. Urol."},{"key":"ref_117","doi-asserted-by":"crossref","first-page":"435","DOI":"10.1007\/s00431-017-2864-5","article-title":"Hypospadias, all there is to know","volume":"176","year":"2017","journal-title":"Eur. J. Pediatr."},{"key":"ref_118","doi-asserted-by":"crossref","first-page":"463","DOI":"10.1016\/j.jpedsurg.2005.11.059","article-title":"Hypospadias: Anatomy, etiology, and technique","volume":"41","author":"Baskin","year":"2006","journal-title":"J. Pediatr. Surg."},{"key":"ref_119","doi-asserted-by":"crossref","first-page":"1953","DOI":"10.1007\/s00431-024-05460-3","article-title":"Creatinine levels in French children with Down syndrome up to ten years old","volume":"183","author":"Pautonnier","year":"2024","journal-title":"Eur. J. Pediatr."},{"key":"ref_120","doi-asserted-by":"crossref","first-page":"2977","DOI":"10.1007\/s00431-021-04078-z","article-title":"Reference serum creatinine levels according to sex, age, and height in children with Down syndrome","volume":"180","author":"Nishino","year":"2021","journal-title":"Eur. J. Pediatr."},{"key":"ref_121","doi-asserted-by":"crossref","first-page":"146709","DOI":"10.1016\/j.gene.2022.146709","article-title":"Effects of genetic ancestry and socioeconomic deprivation on ethnic differences in serum creatinine","volume":"837","author":"Sharma","year":"2022","journal-title":"Gene"},{"key":"ref_122","doi-asserted-by":"crossref","unstructured":"Chuang, G.-T., Tsai, I.-J., and Tsau, Y.-K. (2021). Serum Creatinine Reference Limits in Pediatric Population-A Single Center Electronic Health Record-Based Database in Taiwan. Front. Pediatr., 9.","DOI":"10.3389\/fped.2021.793446"},{"key":"ref_123","doi-asserted-by":"crossref","first-page":"391","DOI":"10.1111\/ped.13525","article-title":"Down syndrome and mild kidney dysfunction","volume":"60","author":"Yamakawa","year":"2018","journal-title":"Pediatr. Int."},{"key":"ref_124","doi-asserted-by":"crossref","first-page":"944","DOI":"10.1111\/ped.14539","article-title":"Is the estimated glomerular filtration rate formula useful for evaluating the renal function of Down syndrome?","volume":"63","author":"Nishino","year":"2021","journal-title":"Pediatr. Int."},{"key":"ref_125","doi-asserted-by":"crossref","first-page":"828","DOI":"10.1016\/S0022-3476(76)81125-0","article-title":"Plasma creatinine and urea concentration in children: Normal values for age and sex","volume":"88","author":"Schwartz","year":"1976","journal-title":"J. Pediatr."},{"key":"ref_126","doi-asserted-by":"crossref","first-page":"629","DOI":"10.1681\/ASN.2008030287","article-title":"New equations to estimate GFR in children with CKD","volume":"20","author":"Schwartz","year":"2009","journal-title":"J. Am. Soc. Nephrol."},{"key":"ref_127","doi-asserted-by":"crossref","first-page":"694","DOI":"10.1007\/s10157-011-0452-y","article-title":"Age, gender, and body length effects on reference serum creatinine levels determined by an enzymatic method in Japanese children: A multicenter study","volume":"15","author":"Uemura","year":"2011","journal-title":"Clin. Exp. Nephrol."},{"key":"ref_128","doi-asserted-by":"crossref","first-page":"155","DOI":"10.4038\/sljch.v46i2.8273","article-title":"Validity of the use of Schwartz formula against creatinine clearance in the assessment of renal functions in children","volume":"46","author":"Dilanthi","year":"2017","journal-title":"Sri Lanka J. Child Health"},{"key":"ref_129","doi-asserted-by":"crossref","first-page":"135","DOI":"10.3343\/alm.2023.0237","article-title":"Exploring Renal Function Assessment: Creatinine, Cystatin C, and Estimated Glomerular Filtration Rate Focused on the European Kidney Function Consortium Equation","volume":"44","author":"Pottel","year":"2024","journal-title":"Ann. Lab. Med."},{"key":"ref_130","doi-asserted-by":"crossref","unstructured":"Huang, Y.-N., Huang, J.-Y., Wang, C.-H., and Su, P.-H. (2023). Long-Term Non-Congenital Cardiac and Renal Complications in Down Syndrome: A Study of 32,936 Patients. Children, 10.","DOI":"10.3390\/children10081351"},{"key":"ref_131","doi-asserted-by":"crossref","first-page":"S1","DOI":"10.1161\/01.cir.0000437738.63853.7a","article-title":"2013 ACC\/AHA Guideline on the Treatment of Blood Cholesterol to Reduce Atherosclerotic Cardiovascular Risk in Adults: A Report of the American College of Cardiology\/American Heart Association Task Force on Practice Guidelines","volume":"129","author":"Stone","year":"2014","journal-title":"Circulation"},{"key":"ref_132","doi-asserted-by":"crossref","first-page":"311","DOI":"10.1038\/35012518","article-title":"The DNA sequence of human chromosome 21","volume":"405","author":"Hattori","year":"2000","journal-title":"Nature"},{"key":"ref_133","doi-asserted-by":"crossref","first-page":"241","DOI":"10.1002\/ajmg.1320140206","article-title":"Down syndrome\u2014A disruption of homeostasis","volume":"14","author":"Shapiro","year":"1983","journal-title":"Am. J. Med. Genet."},{"key":"ref_134","first-page":"293","article-title":"The \u201cgene dosage effect\u201d hypothesis versus the \u201camplified developmental instability\u201d hypothesis in Down syndrome","volume":"57","author":"Pritchard","year":"1999","journal-title":"J. Neural Transm. Suppl."},{"key":"ref_135","doi-asserted-by":"crossref","unstructured":"Duchon, A., and Herault, Y. (2016). DYRK1A, a Dosage-Sensitive Gene Involved in Neurodevelopmental Disorders, Is a Target for Drug Development in Down Syndrome. Front. Behav. Neurosci., 10.","DOI":"10.3389\/fnbeh.2016.00104"},{"key":"ref_136","doi-asserted-by":"crossref","first-page":"eadd6883","DOI":"10.1126\/scitranslmed.add6883","article-title":"Increased dosage of DYRK1A leads to congenital heart defects in a mouse model of Down syndrome","volume":"16","author":"Aoidi","year":"2024","journal-title":"Sci. Transl. Med."},{"key":"ref_137","doi-asserted-by":"crossref","first-page":"dev201077","DOI":"10.1242\/dev.201077","article-title":"Craniofacial dysmorphology in Down syndrome is caused by increased dosage of Dyrk1a and at least three other genes","volume":"150","author":"Redhead","year":"2023","journal-title":"Development"},{"key":"ref_138","doi-asserted-by":"crossref","first-page":"2775","DOI":"10.1093\/hmg\/ddt125","article-title":"Triplication of DYRK1A causes retinal structural and functional alterations in Down syndrome","volume":"22","author":"Laguna","year":"2013","journal-title":"Hum. Mol. Genet."},{"key":"ref_139","doi-asserted-by":"crossref","first-page":"2755","DOI":"10.1038\/s41436-019-0576-0","article-title":"DYRK1A-related intellectual disability: A syndrome associated with congenital anomalies of the kidney and urinary tract","volume":"21","author":"Blackburn","year":"2019","journal-title":"Genet. Med."},{"key":"ref_140","doi-asserted-by":"crossref","unstructured":"Lozic, M., Minarik, L., Racetin, A., Filipovic, N., Saraga Babic, M., and Vukojevic, K. (2021). CRKL, AIFM3, AIF, BCL2, and UBASH3A during Human Kidney Development. Int. J. Mol. Sci., 22.","DOI":"10.3390\/ijms22179183"},{"key":"ref_141","doi-asserted-by":"crossref","unstructured":"Tsygankov, A.Y. (2023). TULA Proteins in Men, Mice, Hens, and Lice: Welcome to the Family. Int. J. Mol. Sci., 24.","DOI":"10.3390\/ijms24119126"},{"key":"ref_142","doi-asserted-by":"crossref","first-page":"109424","DOI":"10.1016\/j.cellsig.2019.109424","article-title":"TULA proteins as signaling regulators","volume":"65","author":"Tsygankov","year":"2020","journal-title":"Cell Signal"},{"key":"ref_143","doi-asserted-by":"crossref","first-page":"274","DOI":"10.1002\/jcp.26890","article-title":"TULA-family proteins: Jacks of many trades and then some","volume":"234","author":"Tsygankov","year":"2018","journal-title":"J. Cell Physiol."},{"key":"ref_144","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1186\/1756-8935-4-7","article-title":"Extensive epigenetic reprogramming in human somatic tissues between fetus and adult","volume":"4","author":"Yuen","year":"2011","journal-title":"Epigenetics Chromatin"},{"key":"ref_145","doi-asserted-by":"crossref","first-page":"979","DOI":"10.1016\/j.ekir.2018.02.006","article-title":"Kidney Transplant Outcomes in 2 Adults With Down Syndrome","volume":"3","author":"Henriksen","year":"2018","journal-title":"Kidney Int. Rep."},{"key":"ref_146","doi-asserted-by":"crossref","first-page":"35","DOI":"10.1159\/000530915","article-title":"Early Recurrence of Immunoglobulin A Nephropathy after Kidney Transplantation in a Patient with Down Syndrome","volume":"147","author":"Ohki","year":"2023","journal-title":"Nephron"},{"key":"ref_147","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1007\/BF02254230","article-title":"Successful living-related renal transplantation in an adolescent with Down syndrome","volume":"9","author":"Edvardsson","year":"1995","journal-title":"Pediatr. Nephrol."}],"container-title":["Genes"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/245\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,9]],"date-time":"2025-10-09T16:38:54Z","timestamp":1760027934000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2073-4425\/16\/3\/245"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,20]]},"references-count":147,"journal-issue":{"issue":"3","published-online":{"date-parts":[[2025,3]]}},"alternative-id":["genes16030245"],"URL":"https:\/\/doi.org\/10.3390\/genes16030245","relation":{},"ISSN":["2073-4425"],"issn-type":[{"value":"2073-4425","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,2,20]]}}}